New Deep Brain Stimulation Area for Parkinson's

A new report in the June issue of Neurology, Neurosurgery & Psychiatry shows that deep brain stimulation targeted to a different brain area can improve the symptoms of Parkinson's disease. Parkinson's disease is a degenerative disorder that usually leads to movement problems. Deep brain stimulation (DBS) involves imlanting a small electrode device inside the brain to send controlled jolts of electricity. For this specific study the researchers targeted the Ventral intermediate (Vim) thalamic region. Previous studies with deep brain stimulation have shown the it can be effective for certain symptoms of parkinson's disease, but improvement in essential tremor have been inconsistent.

The researchers followed the patients with the deep brain stimulation devices for approximately 6.6 years after they underwent surgery. The tremor scores as measured by a common parkinson's rating scale were improved more when the deep brain stimulation device was turned on compared to when it was turned off. Other motor symptoms scores were not improved as much, indicating this treatment is relatively selective in its beneficial effects. This may become a new treatment modality for improving the symptoms of parkinson's disease. You can read the abstract of the study at this site.

Results: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group

Source:
J Neurol Neurosurg Psychiatry 2008;79:694-699

New Gene Therapy Trial for Parkinson's Disease

Oxford Biomedica is planning a gene therapy trial for parkinson's patients. In this trial, researchers will introduce a virus (Lentivector) that will deliver a total of three different genes. These genes encode for three seperate enzymes (tyrosine hydroxylase, GTP-cyclohydrolase 1 and aromatic amino acid decarboxylase) that are involved in the synthesis of the neurotransmitter dopamine. In parkinson's disease, neurons that produce dopamine in an area of the brain called the substantia nigra slowly die off. Parkinson's patients thus have a deficiency of dopamine leading to the symptoms of parkinson's disease such as muscle rigidity, tremor and a slowing of physical movement.

Another successful gene therapy trial had already taken place in the past. In that trial, parkinson's patients had a gene encoding for a protein called glutamic acid decarboxylase (GAD) introduced into their brain via a virus. This specific enzyme synthesizes the neurotransmitter GABA. By increasing GABA in a brain area called the subthalamic nucleus, researchers we're able to reduce specific parkinson's symptoms like uncontrollable tremor. However, GABA deficiency is only a downstream effect of the dopamine deficiency. Increasing GABA in that area of the brain does not get to the source of the problem in parkinson's patients, which is lack of dopamine. So this new trial gets to the source of the problem and may lead to a more robust and long lasting improvement for treatment resistant parkinson's patients. In the future, gene therapy may be used for a variety of other brain based disorders.

Parkinson's Drugs and Gambling

An interesting development, several pharmaceutical companies are being sued over the link between gambling and dopamine agonists. Dopamine agonists are commonly used as a treatment for parkinson's disease but have also been approved for restless leg syndrome.

Drug 'led patients to gamble'

Major drug companies are to be sued over claims that they didn't warn patients quickly enough of the possible bizarre side effects of a drug for Parkinson's Disease. BBCNews


It has been known for several years that dopamine agonist have the potential to cause some adverse effects. These adverse effects include gambling too much (like losing your house), hypersexuality (too much sex, porn etc.) and overeating (like everything in sight). These types of behaviors fall under the innocuous label of "excessive pleasure seeking" and are similar to what happens in bipolar mania/hypomania.

Pramipexole has been shown to reduce levels of anhedonia in both depressed and parkinson's patients. This aspect of pramipexole is likely attributable to its agonist action on postsynaptic D2/D3 receptors in limbic areas of the brain like the nucleus accumbens (the brain's pleasure center). So these drugs may cause a person to seek out pleasurable activities to a greater extent because their reward center is being activated to a greater degree. When this is coupled with the executive dysfunction (poor attention/poor insight etc.) that can be induced by the drug due to understimulation of D1 type receptors in the prefrontal cortex, it could potentially lead to mindless compulsive pleasure seeking. Mindless compulsive pleasure seeking sounds like it's kind of fun, but in reality it has completely destroyed some people's lives. It goes to show you, that experiencing too much pleasure can have a negative impact on your life. Though, there are probably quite a few people who wouldn't mind the drug induced hypersexuality.